Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocytes adhere to cells or extracellular matrices to perform functions relating to cytotoxicity, extravasation and tissue localization, as well as modulation of lymphocyte growth and maturation. This adherence is mainly mediated by 3 families of cell-surface adhesion molecules: integrins, immunoglobulin-related molecules and selectins. Since variations in the degree of adherence may affect the pathophysiology of lymphoproliferative disorders, the expression of a large number of adhesion molecules was analysed on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs), and on EBV-positive or EBV-negative Burkitt's lymphoma (BL) lines, by immunofluorescence flow cytometry and immunoprecipitation with monoclonal antibodies. With regard to the beta 1, beta 2 and beta 3 integrin subfamilies, LCLs strongly expressed CD49d/CD29 (VLA-4), CD11a/CD18 (Leu-CAMa, LFA-1) and CD51/CD61 (vitronectin receptor). These cells also abundantly expressed CD54 (ICAM-1) and CD58 (LFA-3) as well as the "homing receptors" L-selectin (LECAM-1) and CD44. BL lines had considerably lower amounts of VLA-4 than LCLs, and ICAM-1 was expressed only by some of the tumor lines. All other adhesion molecules were absent or minimally expressed in the BL cells.
Int J Cancer 1992 May 28
PMID:Expression of integrins and other adhesion molecules in Epstein-Barr virus-transformed B lymphoblastoid cells and Burkitt's lymphoma cells. 131 64

Mutations of proto-oncogenes and tumor-suppressor genes lead to neoplastic development. Some germline mutations of these genes increase the tumor susceptibility of their carriers, but the relationship between genes controlling tumor susceptibility and the known oncogenes and tumor-suppressor genes remains unelucidated. Moreover, as tumor susceptibility in mouse is controlled by multiple genes, their identification has been virtually impossible. We therefore developed a new system, the recombinant congenic strains (RCS), which separates individual susceptibility genes into different RC strains, thus facilitating their analysis. To map genes controlling the development of colon cancer, we used the Balb/c-c-STS (CcS/Dem) RC strains. Owing to several unidentified genes, Balb/cHeA mice are relatively resistant and STS/A mice highly susceptible to 1,2-dimethylhydrazine-(DMH)-induced colon adenocarcinomas. Each CcS/Dem strain carries a different subset of about 12.5% of genes of the STS strain on the Balb/c background, and individual STS susceptibility genes became segregated into different RC strains. Using CcS-19, one of the highly susceptible RC strains, we mapped a novel colon tumor susceptibility gene, Scc-1, different from the oncogenes and tumor-suppressor genes known to be involved in colon tumorigenesis, in the vicinity of CD44 (Ly-24, Pgp-1) on chromosome 2. The mapping of the Scc-1 gene indicates that the RCS system can be used to map and study the presently unknown genes which control cancer development.
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PMID:Scc-1, a novel colon cancer susceptibility gene in the mouse: linkage to CD44 (Ly-24, Pgp-1) on chromosome 2. 134 18

With increasing emphasis on the early detection of cancer, the search is on for reliable markers that will be clinically helpful in the diagnosis of small tumours and in the assessment of their metastatic potential. This report presents evidence that an abnormal pattern of activity of the CD44 gene is a promising candidate for both of these purposes in various types of malignancy. By a mechanism known as alternative splicing this gene can produce different messenger RNA molecules (transcripts) which are detectable, after amplification, as separate bands in electrophoretic gels. In neoplasia many abnormal variant transcripts are produced. A previous finding in animal experiments, that one such variant might be important in metastasis, prompted our study of human tumour tissue, benign and malignant, and of corresponding normal tissues. We studied tumour tissue from 34 patients with neoplastic disease (mostly breast or colon cancer) and normal or non-malignant diseased breast or colonic tissue from 11 patients and peripheral blood leucocytes from 4 healthy volunteers. CD44 gene activity was studied by amplifying messenger RNA with the polymerase chain reaction (PCR) followed by electrophoresis and blot hybridisation. In malignant tissues there was gross overproduction of each of 9 or more alternatively-spliced large molecular variants in all samples, whereas in the control samples only the standard product was routinely detected with occasional minimal quantities of one or two small variants. Furthermore, the band pattern permitted differentiation between the 23 cases with metastatic tumours of the breast or colon and the 8 with no detectable metastases. Calibration studies seeding blood with tumour cells showed that the technique can detect as few as 10 tumour cells among 10(7) leucocytes (1 ml of blood). Analysis of CD44 splice variants may prove to have applications not just to the early detection of metastatic potential in surgical biopsy specimens but also, if our findings are confirmed, in readily available bodily fluids, to the early diagnosis of cancer in screening programmes, to the assessment of remaining disease in the body and to the early detection of recurrences.
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PMID:Significance of CD44 gene products for cancer diagnosis and disease evaluation. 809 44

Adhesion molecules play an important role in the functioning of the immune system, particularly with regard to cell-cell interactions and antigen presentation. Several adhesion molecules are expressed on Hodgkin's disease-derived cell lines and these are important in their molecular interactions as antigen presenting cells (APC). There are no data regarding the expression of many of these adhesion molecules on Reed-Sternberg cells and its mononuclear variant (Hodgkin's cells (HC)) present in pathological material. To obtain this information we undertook an immunohistological study on material from 18 cases of Hodgkin's disease using a panel of MoAbs to examine the expression of adhesion molecules on HC. The HC were shown to express the integrin beta 1 subfamily molecules, LFA-1 (CD11a) and p150,95 (CD11c) in high density but lacked CR3 (CD11b). All of the immunoglobulin gene superfamily adhesion molecules studied were present to some degree on HC, with ICAM-2, in particular, showing moderate to strong expression in most cases. The Hermes antigen CD44 was present in high density but leukosialin (CD43), another molecule present on diverse leucocyte types, was, in general, not detected on HC. These new data showing that ICAM-1, ICAM-2 and LFA-3 are, like LFA-1, expressed on HC emphasize the ability of HC to act as APC. The known adhesion molecule phenotype of the recently defined haematopoietic lineage of human dendritic cells (DC) is broadly similar to that of HC, perhaps supporting the hypothesis that some HC represent a malignancy of an APC (DC) lineage.
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PMID:Hodgkin's cells express a novel pattern of adhesion molecules. 139 91

A panel of mouse x human B- and T-cell hybrids was analyzed for the expression of MC56 determinant which marks the drug-sensitive state of CEM cells. Karyotypic and phenotypic analyses of the tested clones showed that the expression of MC56 determinant correlated to the presence of human chromosome 11 and segregated concordantly to the epitopes recognized by monoclonal antibodies in the CD44 cluster. By using a particular class of interspecific rodent x human-cell hybrids in which the human genome counterpart is represented in the different clones only by human chromosome 11 or its fragments, we showed that the gene encoding for MC56 determinant is located on the region p13-pter of the short arm of chromosome 11. Therefore, the hypothesized homology between the drug-sensitivity marker MC56 and the CD44 determinant is supported also by gene mapping studies.
Int J Cancer 1992 Oct 21
PMID:The gene encoding for MC56 determinant (drug-sensitivity marker) is located on the short arm of human chromosome 11. 139 41

Cancer metastasis poses the greatest challenge to the eradication of malignancy. The majority of clinical and experimental evidence indicates that metastasis is a non-random, organ-specific process. Tumor cell interaction with endothelium and subendothelial matrix constitutes the most crucial factor in determining the organ preference of metastasis. A plethora of cell surface adhesion molecules, which encompass four major families (i.e., integrins, cadherins, immunoglobulins and selectins) and many other unclassified molecules, mediate tumor-host interactions. Adhesion molecules and adhesion processes are involved in most, if not all, of the intermediate steps of the metastatic cascade. Decreased E-cadherin expression and increased CD44 expression are clearly correlated with the acquisition of the invasive capacity of primary tumor cells. Similarly, altered expression pattern of many other adhesion molecules such as upregulated expression of the laminin receptors and depressed expression of fibronectin receptors (alpha 5 beta 1) appears to be involved in tumor cell invasion into the subendothelial matrix. Tumor cell-endothelium interactions involve several well-defined sequential steps that can be analyzed by the 'Docking and Locking' hypothesis at the molecular level. Tumor cell-matrix interactions are determined by the repertoire of adhesion receptors of tumor cells and the unique composition of organ-specific matrices. Our experimental data, together with others', suggest that the integrin alpha IIb beta 3 is one of the major players in these tumor-host interactions. Tumor-host interaction is a dynamic process which is constantly modulated by a host of factors including various cytokines, growth factors and arachidonate metabolites such as 12(S)-HETE. Delineation of the molecular mechanisms of tumor-host interactions may provide additional means to intervene in the metastatic process.
Cancer Metastasis Rev 1992 Nov
PMID:Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix. 142 22

Human myeloma plasma cells had been considered to express few surface antigens until recently. The past two International Workshops on Leucocyte Differentiation Antigens have shown that myeloma cells can express a range of surface molecules, and it has become clear that many of these have adhesive functions. The identification of ICAM-1 (CD54) and H-CAM (CD44) on human plasma cells was the initial observation, and other antigens such as N-CAM (CD56) and LFA-3 (CD58) have been confirmed as features of malignant plasma cells in particular. The degree of expression of LFA-1 (CD11a) remains to be characterised fully. It seems probable that the loss of some adhesion structures may be associated with increased malignancy and plasma cell leukaemia. At the present time there are few studies relating to the function of these molecules, although homotypic adhesion appears to occur, and it is likely that such studies will shed light on the pathogenesis of myeloma.
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PMID:The role of adhesion molecules in multiple myeloma. 149 Jan 46

A new myeloma cell line designated FLAM-76 was established from a patient with an aggressive nonsecretory plasma cell leukemia. The cell line exhibited morphologic features of flaming cells and contained an abundant eosinophilic cytoplasm with many dilated cisternae of rough endoplasmic reticulum. FLAM-76 cells were positive for cytoplasmic kappa (kapp)-type immunoglobulin but did not secrete it into the culture medium. The cells proliferated in the presence of exogenous interleukin-6 (IL-6) and more than 800 pg/ml of IL-6 was necessary for their continuous growth. The cells did not grow without IL-6, and they did not produce IL-6. Thus, the growth of FLAM-76 appeared to be regulated by the paracrine mechanism of IL-6. Alpha-interferon (alpha-IFN) inhibited the IL-6-dependent growth of FLAM-76 in doses greater than 1000 U/ml. FLAM-76 cells expressed CD38 (OKT10) and cell adhesion-associated antigens such as CD44 and CD54 (ICAM-1). Chromosome analysis revealed FLAM-76 to have a hypodiploid chromosome constitution with t(11;14)(q13;q32) abnormality, which frequently is seen in neoplasms of B-cell origin. Immunoglobulin (JH and Ck) gene rearrangement (but no BCL-1 gene rearrangement) was found in this cell line.
Cancer 1992 Sep 15
PMID:The establishment of an interleukin-6-dependent myeloma cell line (FLAM-76) carrying t(11;14)(q13;q32) chromosome abnormality from an aggressive nonsecretory plasma cell leukemia. 151 3

Expression of the CD44 molecule was examined in a variety of human brain tumours, brain metastases and normal brain. Immunohistological staining with several CD44 antibodies demonstrated differential expression of the CD44 molecule among different brain tumour types. CD44 was strongly expressed in high-grade gliomas and weakly expressed in meningiomas, medulloblastomas and normal brain. Northern blot analysis revealed the presence of 3 major CD44 mRNAs of 1.6, 2.2, and 5.0 kb in glioblastomas and a mRNA of 5.6 kb in meningiomas. CD44 expression was also detected by flow cytometric analysis on cultured cells derived from a variety of human brain tumours including glioblastomas and meningiomas.
Int J Cancer 1992 Feb 20
PMID:Differential expression of the CD44 molecule in human brain tumours. 153 23

A multidrug-resistant cell subline (OV1/VCR) derived from an ovarian adenocarcinoma cell line (OV1/P) was characterized by a typical suppressed malignant phenotype and by a unique karyotypic change: del(11)(p13). In an attempt to discern some genetic alteration of 11p genes that may be relevant to the phenotypic shift, cells were analyzed with DNA probes mapped in the deleted region and with monoclonal antibodies (MoAbs) against 11p-encoded membrane molecules. Southern blot did not detect abnormal restriction patterns of the probed sequences. OV1/VCR cells did not express the CD44 epitope (11p13 MIC4 locus) recognized by the F10-44 MoAb and did not accumulate RNAs of the CD44 (Hermes) core peptide. This defect was not detected in another OV1/P-derived drug-resistant subline that retained the malignant behavior and did not have the del(11p) marker. It may have contributed to phenotypic reversion because evidence shows that CD44 membrane molecule is involved in cell-cell interaction and growth regulation of cancer cells.
Cancer Genet Cytogenet 1992 May
PMID:A multidrug-resistant ovarian carcinoma cell line with a malignant suppressed phenotype is a CD44 gene expression defective mutant. 159 1


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